A Study of LY4257496 in Participants With Cancer (OMNIRAY)

NCT ID: NCT07114601

Last Updated: 2025-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

421 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-06

Study Completion Date

2035-04-30

Brief Summary

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The main purpose of this study is to evaluate safety, tolerability, and efficacy of LY4257496 alone and as part of relevant standard of care (SOC) combination therapy in participants with Gastrin-releasing Peptide Receptor (GRPR)-positive advanced breast, colorectal, prostate, and endometrial cancer. This is a 2-part study. Participation could last up to 36 weeks or until your tumor progresses.

Detailed Description

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Conditions

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Breast Neoplasms Colorectal Neoplasms Prostate Neoplasm Endometrial Neoplasms Neoplasm Metastasis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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LY4257496 Phase 1a Dose Escalation (Cohort A1)

LY4257496 administered intravenously (IV)

Group Type EXPERIMENTAL

LY4257496

Intervention Type DRUG

Administered IV

LY4257496 Phase 1a Dose Optimization (Cohort A2)

LY4257496 administered IV

Group Type EXPERIMENTAL

LY4257496

Intervention Type DRUG

Administered IV

LY4257496 + Standard of Care Phase 1b Cohort B

Tumor specific cohort will receive LY4257496 alone or with standard of care anticancer therapy(ies)

Group Type EXPERIMENTAL

LY4257496

Intervention Type DRUG

Administered IV

Standard of Care Anticancer Therapies

Intervention Type DRUG

Fulvestrant, Imlunestrant, Aromatase Inhibitors, Capecitabine, Abemaciclib

LY4257496 Phase 1b Cohort C

Tumor specific cohort will receive LY4257496

Group Type EXPERIMENTAL

LY4257496

Intervention Type DRUG

Administered IV

LY4257496 Phase 1b Cohort D

Tumor specific cohort will receive LY4257496

Group Type EXPERIMENTAL

LY4257496

Intervention Type DRUG

Administered IV

Interventions

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LY4257496

Administered IV

Intervention Type DRUG

Standard of Care Anticancer Therapies

Fulvestrant, Imlunestrant, Aromatase Inhibitors, Capecitabine, Abemaciclib

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Must have histologically or cytologically proven diagnosis of locally advanced, unresectable, or metastatic cancer.
* Must be assessed by computed tomography (CT)/magnetic resonance imaging (MRI) to confirm at least 1 of the following:

* At least 1 measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* If only bone lesions are present without a soft-tissue component, a bone scan or MRI must confirm at least 2 detectable lesions considered to represent active metastases
* Must have GRPR-positive disease, defined by investigator assessment of GRPR imaging.
* Must have the following histologically or cytologically confirmed diagnosis:

* Estrogen receptor (ER+)/human epidermal growth factor receptor 2 (HER2-) breast cancer
* ER+/HER2+ breast cancer
* Colorectal carcinoma
* Metastatic castration-resistant prostate cancer
* Endometrial carcinoma
* Other GRPR-positive solid tumor
* For participants with breast cancer diagnosis, where possible, ER and HER2 status should be assessed from the most recent tissue biopsy taken at the time of presentation with recurrent or metastatic disease.

* To fulfill the requirement for ER+ disease by local testing, a tumor must express the ER immunohistochemistry, as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
* HER2 status should be determined by local testing, as defined in the relevant ASCO/CAP Guidelines.
* Must have an Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 1.
* Must be able to comply with outpatient treatment, laboratory monitoring, imaging, and required clinic visits for the duration of trial participation.

Exclusion Criteria

* Previously received any radiopharmaceutical. For participants with metastatic castration-resistant prostate cancer (mCRPC), prior 177\^Lu-prostate-specific membrane antigen (PSMA)-617 is permitted.
* Has a history of ongoing acute pancreatitis within 1 year of screening.
* Previously received any prior hemi-body or whole-body radiotherapy, or prior external beam radiation therapy (EBRT) to greater than 25% of the bone marrow.
* A bone superscan, defined as a bone scan that demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint genitourinary tract activity.
* Has evidence of ongoing and untreated urinary tract obstruction or unmanageable urinary incontinence.
* Has known active hepatitis B virus (HBV) (screening for HBV is not required for individuals who do not have a history of HBV, unless required by local regulations). Individuals with treated/chronic HBV are eligible for the trial provided they meet the following criteria:

* Individuals with positive hepatitis B surface antigen (HBsAg) must be on permitted suppressive antiviral therapy prior to C1D1, remain on the same antiviral treatment throughout trial, and should follow local standards for continuation of therapy after completion of trial therapy.
* Undetectable HBV deoxyribonucleic acid (DNA) less than or equal to 28 days of C1D1.
* Has known active hepatitis C virus (HCV) (screening for HCV is not required for individuals who do not have a history of HCV unless required by local regulations). Individuals previously treated for HCV are eligible for the trial provided they meet the following criteria:

* Completion of curative antiviral therapy.
* HCV viral load below the limit of quantification less than or equal to 28 days of C1D1.
* Negative hepatitis C antibody result OR, if positive, then must be hepatitis C RNA negative.
* Has known untreated human immunodeficiency virus (HIV) infection (screening for HIV is not required unless required by local regulations). Participants on permitted antiretroviral therapy (ART) and who have well-controlled HIV infection/disease are eligible provided they meet the following criteria:

* Must be on a stable and permitted ART regimen without changes in drug or dose, for at least 4 weeks prior to C1D1 and have a viral load of \<400 copies per mL prior to less than or equal to 28 days of C1D1.
* CD4+ T-cell count greater than or equal to 350 cells/uL less than or equal to 28 days of C1D1.
* Has an active second malignancy unless in remission with life expectancy greater than 2 years.
* Has known hypersensitivity to any component or excipient of LY4257496.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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City of Hope

Duarte, California, United States

Site Status NOT_YET_RECRUITING

University of California, Los Angeles (UCLA)

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

Stanford University Medical Center

Stanford, California, United States

Site Status RECRUITING

Biogenix Molecular, LLC

Miami, Florida, United States

Site Status RECRUITING

Emory University School of Medicine - Winship Cancer Institute

Atlanta, Georgia, United States

Site Status NOT_YET_RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status NOT_YET_RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status NOT_YET_RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status NOT_YET_RECRUITING

BAMF Health Inc.

Grand Rapids, Michigan, United States

Site Status RECRUITING

Washington University

St Louis, Missouri, United States

Site Status NOT_YET_RECRUITING

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status NOT_YET_RECRUITING

Texas Oncology - DFW (Sammons CC)

Dallas, Texas, United States

Site Status NOT_YET_RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status NOT_YET_RECRUITING

Juravinski Cancer Centre

Hamilton, , Canada

Site Status NOT_YET_RECRUITING

Lady Davis Institute for Medical Research Jewish General Hospital

Montreal, , Canada

Site Status NOT_YET_RECRUITING

Sunnybrook Health Sciences Centre

Toronto, , Canada

Site Status NOT_YET_RECRUITING

Princess Margaret Hospital

Toronto, , Canada

Site Status RECRUITING

Institut de Cancerologie de l'Ouest - site St-Herblain

Saint-Herblain, , France

Site Status NOT_YET_RECRUITING

Universitaetsklinikum Essen

Essen, , Germany

Site Status NOT_YET_RECRUITING

LMU Klinikum Muenchen-Campus Grosshadern

München, , Germany

Site Status NOT_YET_RECRUITING

Hospital Universitari Quiron Dexeus Barcelona

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Countries

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United States Canada France Germany Spain

Central Contacts

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Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

Role: CONTACT

1-317-615-4559

Physicians interested in becoming principal investigators please contact

Role: CONTACT

Related Links

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https://trials.lilly.com/en-US/trial/637755

A Study of LY4257496 in Participants With Cancer (OMNIRAY)

Other Identifiers

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J6C-OX-JKFA

Identifier Type: OTHER

Identifier Source: secondary_id

27354

Identifier Type: -

Identifier Source: org_study_id

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